Process for the preparation of beta-naphthoquinone semicarbazone

ABSTRACT

A process for the preparation of Beta -naphthoquinone semicarbazone, which comprises reacting an aqueous solution of semicarbazide hydrochloride with a boiling ethanolic solution of Beta -naphthoquinone and taking care that the relative amounts of water and ethanol in the reaction mixture be in a volume ratio of from 40:100 to 360:100. In this way, the Beta -naphthoquinone semicarbazone is obtained with great purity and high yield.

United States Patent 1 Beaudet [451 Sept. 11, 1973 [54] PROCESS FOR THEPREPARATION OF BETA-NAPHTHOQUINONE SEMICARBAZONE [76] Inventor: CamilleAlphonse Beaudet, Avenue A. Lancaster. 86 Uccle. Belgium [22] Filed:July 23, 1971 211 Appl. No.: 165,399

OTHER PUBLlCATlONS Merck Index, 1968, p. 717

Primary ExaminerVivian Garner Attorney-Irvin S. Thompson and Robert 1.Patch 5 7 ABSTRACT A process for the preparation of B-naphthoquinonesemicarbazone, which comprises reacting an aqueous solution ofsemicarbazide hydrochloride with a boiling ethanolic solution ofB-naphthoquinone and taking care that the relative amounts of water andethanol in the reaction mixture be in a volume ratio of from 40:100 to3601100.

In this way, the B-naphthoquinone semicarbazone is obtained with greatpurity and high yield.

4 Claims, No Drawings PROCESS FOR THE PREPARATION OFBETA-NAPIITIIOQUINONE SEMICARBAZONE BACKGROUND OF THE INVENTION Thisinvention relates to improvements to the preparation of finaphthoquinone semicarbazone which is a known compound having hemostaticproperties.

It is known to prepare B-naphthoquinone semicarbazone by a process inwhich B-naphthoquinone is dissolved in 96% ethanol at a temperature ofabout 50C, semicarbazide hydrochloride is then added to the obtainedsolution of fi-naphthoquinone, the amount of added semicarbazidehydrochloride being less than equirnolar in respect of the amount ofB-naphthoquinone, the obtained mixture is thereafter stirred during 45minutes at 50C and then cooled at 3C. B-naphthoquinone semicarbazonemelting at 182-1 84C is finally recovered by filtration. Yie1d:59%.

SUMMARY OF THE INVENTION It has now been found that it is possible toobtain fi-naphthoquinone semicarbazone with a substantially higher yieldand a much betterpurity when the reaction conditions of the knownprocess are modified as described hereafter.

It has been discovered that these improved results may be surprisinglyobtained when an aqueous solution of the semicarbazide hydrochloride isadded to a boiling ethanolic solution of fi-naphthoquinone.

In respect of the yield of B-naphthoquinone semicarbazone, a maximum ofabout 80% is obtained when the volume ratio of waterzethanol is betweenabout 40:100 and about 360:100.

DETAILED DESCRIPTION OF THE INVENTION In other words, fi-naphthoquinonesemicarbazone is obtained with a yield of about 80% when an aqueoussolution of semicarbazide hydrochloride is added to a boiling ethanolicsolution of B-naphthoquinone, the amount of water present in thereaction mixture being between about 40 and 360 parts by volume for 100parts by volume of pure ethanol.

In respect of the purity of the B-naphthoquinone semicarbazone, it hasbeen found that a maximum of 100% is obtained when the volume ratio ofwater:ethanol is of about 40:100. This means that 100% pureB-naphthoquinone semicarbazone is obtained when an aqueous solution ofsemicarbazide hydrochloride is reacted with an ethanolic solution ofB-naphthoquinone the amount of water present in the reaction mixturebeing of about 40 parts by volume for 100 parts by volume of pureethanol.

It has also been found that it is advantageous to use an excess ofsemicarbazide hydrochloride with regard to the molar amount ofB-naphthoquinone, this excess being of at least 1% by weight andpreferably of -1 to 5%.

This invention relates therefore to a process for preparingfl-naphthoquinone semicarbazone, by reacting semicarbazide hydrochloridewith B-naphthoquinone, said process being characterized by the fact thatan aqueous solution of semicarbazide hydrochloride is reacted with aboiling ethanolic solution of fl-naphthoquinone, the amounts of waterandethanol present in the reaction mixture being such that the volume ratioof water:ethanol is between about 405100 and 3602100, said ratio beingpreferably of about 40:100.

The aqueous solution of semicarbazide hydrochloride is preferably slowlyadded to the boiling ethanolic solution of B-naphthoquinone and thereaction mixture is allowed to cool to the room temperature while beingstirred. The reaction mixture is then kept at a tempera- EXAMPLE 1 0.5 g(0.00318 mole) of B-naphthoquinone are dissolved in 10 ml of boiling 96%ethanol. An aqueous solution of 0.368 g (0.0032 mole) of semicarbazidehydrochloride in 18 ml of water at a temperature of about 60C is thenslowly added to the B-naphthoquinone ethanolic solution. The volumeratio of waterzethanol in the reaction mixture is of about 180/ 100.When the addition of the aqueous solution of semicarbazide hydrochloridehas been completed, the reaction mixture is allowed to cool, while beingstirred. The reaction mixture is then kept in a refrigerator at about 4Cduring several hours (8 to 10 hours). 28 ml of water are then added tothe reaction mixture which is then filtered so as to separate theprecipitate of fi-naphtho quinone semicarbazone. This precipitate isfinally filtered, washed with water and dried. 0.55 g ofB-naphthoquinone semicarbazone having a purity of 94.5% and melting at185,C are obtained. Yield: 81%.

EXAMPLES 2 to 6 The method described in example 1 is used except thatvarious amounts of water and ethanol are used.

The following table gives the purity and the yield of B-naphthoquinonesemicarbazone, as well as the approximate volume ratio of watercethanolin the'reaction mixture. The results obtained in example 1 are alsomentioned in the following table.

TABLE Exam- Amount Amount Volume ratio B-naphthoquiple of ethaof waterwaterzethanol none semicar- No. nol used used bazone (ml) (ml) YieldPurity 2 24 4 16: 100 100 3 20 8 40:100 4 l4 l4 100:100 81 97 1 l0 l8:100 81 94.5 5 6 22 360:100 83 86.8

ln examples 1 to 6, the purity of the obtained B-naphthoquinonesemicarbazone has been determined by measuring the optical density inthe presence of ammonia at 490 nm (in respect of a reference sample).

The precipitate obtained in example 6 comprises essentially non-reactedB-napththoquinone.

In respect of both the yield and purity of the obtained B-naphthoquinonesemicarbazone, the above table shows clearly that the optimum operatingconditions are those where the reaction mixture contains water andalcohol in a volume ratio of about 40:100.

1 claim:

1. A process for preparing B-naphthoquinone semicarbazone by reactingsemicarbazide hydrochloride with B-naphthoquinone, characterized by thefact that an aqueous solution of semicarbazide hydrochloride is reactedwith a boiling ethanolic solution of B-napththoquinone, the amounts ofwater and ethanol present in the reaction mixture being such that thevolume ratio of waterzethanol is between about 40: I and 360:100.

2. A process according to claim 1, characterized by;

the fact that the waterzethanol volume ratio is of about,

3. A process according to claim 1, characterized by 4. A processaccording to claim 3, characterized by the fact that said excess is of1% to 5% by weight.

0 a: a: Y 1: a a:

2. A process according to claim 1, characterized by the fact that thewater:ethanol volume ratio is of about 40:100.
 3. A process according toclaim 1, characterized by the fact that an excesS of at least 1% byweight of semicarbazide hydrochloride with regard to the amount of Beta-naphthoquinone is used.
 4. A process according to claim 3,characterized by the fact that said excess is of 1% to 5% by weight.